Effect of diuretics and sodium-restricted diet on sleep apnea severity: study protocol for a randomized controlled trial

BACKGROUND: Obstructive sleep apnea occurs as a result of increased collapsibility of the upper airway. Overnight fluid displacement from the legs to the neck causes pharyngeal narrowing and increased apnea severity. Sodium intake is associated with apnea severity. We hypothesized that interventions that decrease bodily fluid content might reduce the severity of sleep apnea. METHODS/DESIGN: This is a randomized clinical trial including men with an apnea-hypopnea index greater than 30 events/hour, previously diagnosed by full-night in-laboratory polysomnography. A total of 54 men will be included and randomly assigned to three groups: Diuretic (n = 18), sodium-restricted diet (n = 18), and control (n = 18). The intervention will last one week. Intention-to-treat and per-protocol analyses will be performed. The diuretic group will receive combined spironolactone 100 mg plus furosemide 20 mg daily, taken in the morning. The diet group will receive a regimen with a maximum intake of 3 g of sodium per day. The control group will receive a placebo pill and will maintain all eating habits while keeping a recall diary of their dietary behavior. The primary outcome measure will be change in apnea-hypopnea index. The secondary outcome measures will be variations of: anthropometric and bioelectrical impedance variables, office blood pressure, respiratory variables from in-home level III polysomnography, excessive daytime sleepiness, glycolipid profile, C-reactive protein, 24 h urinary variables, and adverse events. DISCUSSION: Despite the high efficacy of continuous positive airway pressure to reverse upper airway obstruction in sleep apnea, partial adherence to this form of treatment reduces its efficiency. Thus, additional forms of treating apnea need to be investigated. If the results of this proof-of-concept trial show that decreases in bodily fluid content, either by diuretic or dietary intervention, reduces the severity of sleep apnea, further investigation will be necessary before these results can be translated and adopted as an adjunct apnea therapy. TRIAL REGISTRATION: clinicaltrials.gov NCT01945801.